TY - JOUR
T1 - Asymmetric localization of Vangl2 and Fz3 indicate novel mechanisms for planar cell polarity in mammals
AU - Montcouquiol, Mireille
AU - Sans, Nathalie
AU - Huss, David
AU - Kach, Jacob
AU - David Dickman, J.
AU - Forge, Andrew
AU - Rachel, Rivka A.
AU - Copeland, Neal G.
AU - Jenkins, Nancy A.
AU - Bogani, Debora
AU - Murdoch, Jennifer
AU - Warchol, Mark E.
AU - Wenthold, Robert J.
AU - Kelley, Matthew W.
PY - 2006
Y1 - 2006
N2 - Planar cell polarity (PCP) is a process in which cells develop with uniform orientation within the plane of an epithelium. To begin to elucidate the mechanisms of PCP in vertebrates, the localization of the protein Vangl2 (Van Gogh-like) was determined during the development of the mammalian cochlea. Results indicate that Vangl2 becomes asymmetrically localized to specific cell- cell boundaries along the axis of polarization and that this asymmetry is lost in PCP mutants. In addition, PDZ2 (postsynaptic density/Discs large/zona occludens 1), PDZ3, and PDZ4 of the PCP protein Scrb1 (Scribble) are shown to bind to the C-terminal PDZ binding domain of Vangl2, suggesting that Scrb1 plays a direct role in asymmetric targeting of Vangl2. Finally, Fz3 (Frizzled), a newly demonstrated mediator of PCP, is also asymmetrically localized in a pattern that matches that of Vangl2. The presence and asymmetry of Fz3 at the membrane is shown to be dependent on Vangl2. This result suggests a role for Vangl2 in the targeting or anchoring of Fz3, a hypothesis strengthened by the existence of a physical interaction between the two proteins. Together, our data support the idea that protein asymmetry plays an important role in the development of PCP, but the colocalization and interaction of Fz3 and Vangl2 suggests that novel PCP mechanisms exist in vertebrates.
AB - Planar cell polarity (PCP) is a process in which cells develop with uniform orientation within the plane of an epithelium. To begin to elucidate the mechanisms of PCP in vertebrates, the localization of the protein Vangl2 (Van Gogh-like) was determined during the development of the mammalian cochlea. Results indicate that Vangl2 becomes asymmetrically localized to specific cell- cell boundaries along the axis of polarization and that this asymmetry is lost in PCP mutants. In addition, PDZ2 (postsynaptic density/Discs large/zona occludens 1), PDZ3, and PDZ4 of the PCP protein Scrb1 (Scribble) are shown to bind to the C-terminal PDZ binding domain of Vangl2, suggesting that Scrb1 plays a direct role in asymmetric targeting of Vangl2. Finally, Fz3 (Frizzled), a newly demonstrated mediator of PCP, is also asymmetrically localized in a pattern that matches that of Vangl2. The presence and asymmetry of Fz3 at the membrane is shown to be dependent on Vangl2. This result suggests a role for Vangl2 in the targeting or anchoring of Fz3, a hypothesis strengthened by the existence of a physical interaction between the two proteins. Together, our data support the idea that protein asymmetry plays an important role in the development of PCP, but the colocalization and interaction of Fz3 and Vangl2 suggests that novel PCP mechanisms exist in vertebrates.
KW - Cochlea
KW - Frizzled
KW - Inner ear
KW - Mechanosensory hair cell
KW - Planar polarity
KW - Stereociliary bundle
KW - Van Gogh
UR - http://www.scopus.com/inward/record.url?scp=33646941288&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4680-05.2006
DO - 10.1523/JNEUROSCI.4680-05.2006
M3 - Article
C2 - 16687519
AN - SCOPUS:33646941288
SN - 0270-6474
VL - 26
SP - 5265
EP - 5275
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 19
ER -